The Aryl hydrocarbon Receptor (AhR) interacts with c-Maf to promote the differentiation of IL-27-induced regulatory type 1 (T(R)1) cells

IL-10 producing regulatory type 1 (T(R)1) T cells are instrumental in the prevention of tissue inflammation, autoimmunity and graft-versus-host disease. The transcription factor c-Maf is essential for T(R)1 induction of IL-10, but the molecular mechanisms leading to the development of these cells remain incompletely understood. We demonstrate that the ligand–activated transcription factor aryl hydrocarbon receptor (AhR) induced by IL-27, synergizes with c-Maf to promote the development of T(R)1 cells. Upon T cell activation under T(R)1-skewing conditions, the AhR binds to c-Maf and promotes the transactivation of both Il10 and Il21 promoters, resulting in the generation of T(R)1 cells and amelioration of experimental autoimmune encephalomyelitis. Manipulation of AhR signaling could therefore be beneficial in the resolution of excessive inflammatory responses.